The effects of pyridoxine on pituitary hormone secretion in amenorrhea-galactorrhea syndromes

Six patients with amenorrhea, five of whom had galactorrhea and elevated PRL levels, were evaluated on a metabolic ward. All had normal sella tomograms, normal thyroid functions, and routine laboratory evaluations. None of the patients had taken any medication in the previous 6 months. On alternate days, five patients received 500 microgram of TRH iv with the measurement of PRL, TSH, FSh, LH, and hGH; 500 mg L-dopa orally with the measurement of PRL, FSH, and LH; a bolus infusion of 300 mg pyridoxine (B6) with measurement of PRL, hGH, TSH, FSH, and LH; and 25 mg chlorpromazine (CPZ) im with the measurement of PRL, LH, and FSH. The patients were then discharged on 600 mg oral pyridoxine/day and were readmitted for a repeat of the complete protocol 21 days later. The patients were continued on 600 mg oral pyridoxine for 3-4 months with monthly evaluations of serum PRL, LH, and FSH levels. These evaluations continued for 3 months after discontinuing pyridoxine. There was no demonstrable change in serum PRL after acute or chronic B6 therapy, mor was there a significant change in the response of PRL to CPZ, L-dopa, or TRH. The mean basal PRL was 97.5 +/- 9.7 ng/ml and after 3-4 months of oral pyridoxine was 97.1 +/- 14.8. In addition, there was no significant change in LH or FSH levels in response to acute or chronic B6, TRH, L-dopa, or CPZ. Neither acute B6 infusion nor chronic B6 therapy had any effect on TSH or the TSH response to TRH. Finally, acute B6 infusion had no effect on hGH levels and there were no paradoxical hGH responses to TRH. Two patients began having regular menses while on chronic pyridoxine. Their hormonal responses did not differ from those of the group, however.     

Behavior of basal and stimulated serum levels of prolactin, growth hormone and gonadotropins in females with chronic uremia

In 11 female patients with chronic uraemia at the age of 20 to 47 years (average age: 33.1 years) the behaviour of basal and stimulated serum levels of prolactin (PRL), growth hormone (HGH) and gonadotropins (LH, FSH) was investigated. For stimulation of the hormone secretion a sequential test with arginine hydrochloride, gonadotropin releasing hormone (GnRH) and thyrotropin releasing hormone (TRH) was used. In 2 women the investigations were repeated after kidney transplantation. The determination of LH, FSH, PRL and HGH was performed radioimmunologically. The investigations show that in women with chronic uraemia the basal LH-levels in general lie clearly above of those ones of women with biphasic cycles, whereas the FSH-levels are not increased. The LH-response after administration of 25 micrograms GnRH is adequate in 6 women and is absent in 5 women. After kidney transplantation a clear reduction of the basal LH-levels in comparison to the preliminary values is to be established. The increased basal LH-levels are causally made responsible for the disturbances of the menstrual cycle in women with chronic uraemia. For PRL hyper- and normoprolactinaemic as well as hypoprolactinaemic basal levels are found. A connection between the height of the PRL and creatinine levels cannot be proved. Apart from a adequate PRL response to the stimulation with TRH in the individual case this response is inadequate or is absent. The basal HGH-levels are in the area of reference. In all women HGH can adequately be stimulated, whereby the case in question is presumably a so-called paradoxical TRH-effect.     

LACK OF EFFECT OF THE TRH RELATED DIPEPTIDE HISTIDYL-PROLINE DIKETOPIPERAZINE ON TSH AND PRL SECRETION IN NORMAL SUBJECTS, IN PATIENTS WITH MICROPROLACTINOMAS AND IN PRIMARY HYPOTHYROIDISM

We have studied the effects of the TRH related dipeptide histidyl-proline diketopiperazine [cyclo (His-Pro)] on basal and stimulated TSH and PRL secretion in normal volunteers, in patients with microprolactinomas and in patients with primary hypothyroidism. Cyclo (His-Pro), 400 micrograms intravenously did not alter basal TSH or PRL levels in normal males and females and was also without effect upon the elevated basal TSH and PRL levels in patients with primary hypothyroidism and microprolactinomas respectively. The same dose of cyclo (His-Pro) did not affect the TSH or PRL response to TRH (100 micrograms i.v.) in normal male volunteers. These data indicate that cyclo (His-Pro) does not affect TSH and PRL secretion in man at this dosage. It is also unlikely that this molecule will be of any therapeutic benefit in states of hyperprolactinaemia.     

Prolactin and TSH responses to TRH, chlorpromazine and L-dopa in children with human growth hormone deficiency.

Prolactin (PRL) and TSH responses to TRH, chlorpromazine (CPZ) and L-DOPA were studied in 23 children (15 male and 8 female) with human growth hormone (HGH) deficiency. Eight patients (group I) showed normal PRL response to TRH and CPZ but TSH response to TRH was delayed in 4 of this group. Twelve patients (group II) had normal (4 patients) or higher (8 patients) baseline PRL level and showed lower PRL response to CPZ than that to TRH. TSH response to TRH was normal in 3, blunted in 1, and delayed in 8 patients. Three patients (group III) had no PRL response to either TRH or CPZ. TSH response to TRH was normal in 1 but blunted in 2 patients. Of 8 patients with a higher baseline PRL level (group II and III), L-DOPA suppressed PRL secretion to less than 50% of the initial value in 7 patients, but not in 1 patient, in whom the diagnosis of hypothalamic tumour was established on brain surgery following these examinations. These results suggest that hypothalamic disorders are involved in more than half of 23 children with HGH deficiency.     

Effect of cyproheptadine on thyrotrophin and prolactin secretion in normal man.

In order to investigate the effect of cyproheptadine, a compound with antiserotoninergic activity, on the secretion of thyrotrophin (TSH) and prolactin (PRL), the nocturnal secretory patterns of these hormones have been studied in 4 normal men in the basal state and after an oral treatment with the drug. In addition, the TSH and PRL responses to TRH of 6 women were compared in the basal conditions and after cyproheptadine treatment. The TSH nocturnal secretion was slightly modified by drug treatment. The response to TRH as well as the basal levels were comparable in the treated and non-treated subjects. In contrast, the PRL secretion measured through the nocturnal investigation was significantly inhibited by cyproheptadine administration as were the PRL basal levels in the TRH test. The PRL response to TRH was comparable in both situations.     

Effect of lysine vasopressin on basal and TRH stimulated TSH and PRL release in normal men

In order to test the possible effects of lysine vasopressin (LVP) on basal and TRH stimulated TSH and PRL release, an iv bolus of LVP (0.06 IU/kg bw) was injected alone or just before TRH (20 or 400 micrograms iv) in 18 normal male subjects. The administration of LVP modified neither the basal secretion of TSH and PRL nor the TSH and PRL release induced by 20 or 400 micrograms TRH. These data suggest that in humans, vasopressin is not involved in the control of TSH and PRL release at the anterior pituitary level.     

Thyrotropin-releasing hormone stimulates growth hormone release from the anterior pituitary of hypothyroid rats in vitro

We have examined the interaction of thyroid hormone and TRH on GH release from rat pituitary monolayer cultures and perifused rat pituitary fragments. TRH (10(-9) and 10(-8)M) consistently stimulated the release of TSH and PRL, but not GH, in pituitary cell cultures of euthyroid male rats. Basal and TRH-stimulated TSH secretion were significantly increased in cells from thyroidectomized rats cultured in medium supplemented with hypothyroid serum, and a dose-related stimulation of GH release by 10(-9)-10(-8) M TRH was observed. The minimum duration of hypothyroidism required to demonstrate the onset of this GH stimulatory effect of TRH was 4 weeks, a period significantly longer than that required to cause intracellular GH depletion, decreased basal secretion of GH, elevated serum TSH, or increased basal secretion of TSH by cultured cells. In vivo T4 replacement of hypothyroid rats (20 micrograms/kg, ip, daily for 4 days) restored serum TSH, intracellular GH, and basal secretion of GH and TSH to normal levels, but suppressed only slightly the stimulatory effect of TRH on GH release. The GH response to TRH was maintained for up to 10 days of T4 replacement. In vitro addition of T3 (10(-6) M) during the 4-day primary culture period significantly stimulated basal GH release, but did not affect the GH response to TRH. A GH stimulatory effect of TRH was also demonstrated in cultured adenohypophyseal cells from rats rendered hypothyroid by oral administration of methimazole for 6 weeks. TRH stimulated GH secretion in perifused [3H]leucine-prelabeled anterior pituitary fragments from euthyroid rats. A 15-min pulse of 10(-8) M TRH stimulated the release of both immunoprecipitable [3H]rat GH and [3H]rat PRL. The GH release response was markedly enhanced in pituitary fragments from hypothyroid rats, and this enhanced response was significantly suppressed by T4 replacement for 4 days. The PRL response to TRH was enhanced to a lesser extent by thyroidectomy and was not affected by T4 replacement. These data suggest the existence of TRH receptors on somatotrophs which are suppressed by normal amounts of thyroid hormones and may provide an explanation for the TRH-stimulated GH secretion observed clinically in primary hypothyroidism.     

Serum thyrotropin and prolactin in the syndrome of generalized resistance to thyroid hormone: responses to thyrotropin-releasing hormone stimulation and short term triiodothyronine suppression

Serum TSH and PRL levels and their response to TRH were measured in 11 patients with generalized resistance to thyroid hormone (GRTH), 6 euthyroid subjects, and 6 patients with primary hypothyroidism. TSH and PRL levels and their response to TRH were also measured after the consecutive administration of 50, 100, and 200 micrograms T3 daily, each for a period of 3 days. Using a sensitive TSH assay, all GRTH patients had TSH values that were elevated or within the normal range. On the basis of a normal or elevated TSH level, GRTH patients were classified as GRTH-N1 TSH (5 patients) or GRTH-Hi TSH (6 patients), respectively. Only GRTH patients with previous thyroid ablative therapy had basal TSH values greater than 20 mU/L. TSH responses, in terms of percent increment above baseline, were appropriate for the basal TSH level in all subjects. No GRTH patient had an elevated basal PRL level. PRL responses to TRH were significantly increased only in the hypothyroid controls compared to values in all other groups. On 50 micrograms T3, 7 of 12 (58%) nonresistant (euthyroid and hypothyroid) and 1 of 11 (9%) resistant subjects had a greater than 75% suppression of the TSH response to TRH. On the same T3 dose, 2 of 12 (17%) nonresistant and 4 of 11 (36%) resistant subjects had a greater than 50% suppression of the PRL response to TRH. On 200 micrograms T3, all subjects, except for 1 with GRTH, had a greater than 75% suppression of the TSH response to TRH. On the same T3 dose, while 11 of 12 (92%) nonresistant subjects had a greater than 50% reduction of the PRL response to TRH, only 3 of 10 (30%) resistant patients showed this degree of suppression (P less than 0.005). Without previous ablative therapy, serum TSH in patients with GRTH is usually normal or mildly elevated. The TSH response to TRH is proportional to the basal TSH level and is suppressed by exogenous T3. However, on 200 micrograms T3 basal TSH was not detectable (less than 0.1 mU/L) in all euthyroid subjects, but it was measurable in three of four GRTH patients with normal TSH levels before T3 treatment. PRL levels in GRTH are normal even when TSH is elevated. The PRL response to TRH is not increased in GRTH. In all subjects, exogenous T3 suppresses the PRL response to TRH to a lesser degree than the TSH response, but this difference is much greater in patients with GRTH.     

THE EFFECT OF LISURIDE HYDROGEN MALEATE, AN ERGOT DERIVATIVE ON ANTERIOR PITUITARY HORMONE SECRETION IN MAN

The effects of single oral doses of 0.2 mg of lisuride hydrogen maleate, a semisynthetic ergot derivative, on serum levels of prolactin (PRL), growth hormone (GH), thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), cortisol and blood glucose were studied in six normal males. Lisuride effectively inhibited basal PRL secretion as well as the PRL response to TRH given 3 h later. In addition, the drug raised basal GH levels and decreased basal and TRH stimulated TSH secretion. No significant differences between lisuride and control were observed in basal LH and FSH, LHRH stimulated gonadotrophins or in cortisol. Drowsiness was noted by all subjects, one became nauseated and another vomited, 60 and 90 min respectively after administration of lisuride. No changes were seen in pulse rate and blood pressure. The endocrine effects of lisuride were attenuated by the prior administration of the dopamine antagonist metoclopramide. These results suggest that lisuride acts as a long-acting dopamine agonist and that therefore this drug could be of therapeutic use in hyperprolactinaemic states and acromegaly.     

Pyridostigmine and metoclopramide do not restore the TSH response to TRH inhibited by L-thyroxine treatment in children with goiter

To define the role of somatostatin and dopamine in TSH suppression induced by L-thyroxine, 16 children (12 F, 4 M) on suppressive doses of L-thyroxine (3-4 microg/kg/day) for endemic goiter were studied. Firstly a conventional TRH test was performed in all subjects, in order to evaluate TSH, PRL and GH (basal study). A week later a second TRH test was carried out; one hour before the test, however, group A (9 patients) was given 60 mg pyridostigmine bromide po (pyridostigmine study) and group B (7 patients) 10 mg metoclopramide po (metoclopramide study). In the basal study, TSH was suppressed in both groups and levels did not increase following TRH administration, while PRL increased significantly and GH levels remained stable. In the pyridostigmine study, TSH levels did not increase following TRH administration, while PRL and GH levels were both significantly raised. In the metoclopramide study, TSH and GH levels were not raised following TRH administration, while a significantly greater increase of PRL was observed. In conclusion, suppressive doses of L-thyroxine inhibit the TSH response to TRH, while they do not seem to affect GH and PRL secretion. Somatostatin and/or dopamine do not seem to play a significant role in the L-thyroxine-induced TSH suppression.     

THYROTROPHIN, PROLACTIN AND GROWTH HORMONE RESPONSES TO TRH IN BARBITURATE COMA AND IN DEPRESSION

The effects of 200 microgram thyrotrophin-releasing hormone (TRH) i.v. on thyrotrophin (TSH), prolactin (PRL), growth hormone (GH) and triiodothyronine (T3) were studied in eight patients with barbiturate coma due to attempted suicide, in the same patients after recovery, in eight depressive patients and in eight normal controls. The patients with barbiturate coma presented normal basal TSH and PRL, elevated basal GH and normal PRL but blunted TSH responses to TRH; their GH concentrations varied widely without consistent relation to TRH administration. The same patients after recovery from coma presented normal TSH and PRL, slightly elevated basal GH, and normal PRL but blunted TSH responses to TRH; in four of these patients, a clear-cut rise in GH (i.e. more than 10 ng/ml) occurred after TRH administration. The depressive patients presented normal basal TSH and PRL, slightly elevated basal GH, and normal PRL but blunted TSH responses to TRH; in four of these patients, a moderated rise in GH (less than 10 ng/ml) occurred after TRH administration. The increment in T3 concentrations 120 min after TRH was found reduced in the comatose patients only. Basal cortisol was measured in all the subjects and found elevated in the comatose patients only. It is concluded that the abnormal TSH and GH responses to TRH observed in patients with barbiturate coma are more likely related to depressive illness than to an effect of barbiturates at the pituitary level. Barbiturates might affect thyroid secretion.     

EFFECT OF FENOLDOPAM, A DOPAMINE D-1 RECEPTOR AGONIST, ON PITUITARY, GONADAL AND THYROID HORMONE SECRETION

The influence of fenoldopam, a dopamine (DA) D-1 receptor agonist, on basal and GnRH/TRH stimulated PRL, GH, LH, TSH, testosterone and thyroid hormone secretion was studied in nine normal men. All men received 4-h infusions of either 0.9% saline or fenoldopam at an infusion rate of 0.5 microgram/kg min, 12-16 ml/h, adjusted according to weight. After 3 h of infusion, 50 micrograms GnRH and 100 micrograms TRH was given i.v. Blood samples were collected every 15 min from 1 h before to 1 h after the infusion for a total of 6 h for measurements of PRL, LH, FSH, GH, TSH, testosterone, T4 and T3. The median PRL concentration increased significantly (P less than 0.01) to 128%, range 87-287, of preinfusion levels, compared to the decline during control infusion (85%, 78-114). Basal TSH levels declined significantly to 71% (60-91) during fenoldopam compared with 82% (65-115) during control infusion (P less than 0.05). Basal LH, FSH, GH and thyroid hormones were similar during fenoldopam and control infusions (P greater than 0.05). The LH response to GnRH/TRH was significantly (P less than 0.02) increased by fenoldopam infusion. Basal and stimulated testosterone concentration was lower during fenoldopam (P less than 0.01) infusion compared with control. Other hormones were similar after GnRH/TRH stimulation during fenoldopam and saline infusions. These results suggest that DA D-1 receptors are involved in the modulation of pituitary hormone secretion. We suggest that the effect of fenoldopam on PRL and TSH is mainly at the hypothalamic level. Regarding the effect on LH concentrations, an additional direct effect of fenoldopam on testosterone regulation can not be excluded.     

Prolactin response to growth hormone-releasing hormone during chronic thyrotropin-releasing hormone infusion in the treatment of amyotrophic lateral sclerosis

In six patients suffering from amyotrophic lateral sclerosis we evaluated changes of T4, T3, TSH, PRL, and GH during treatment by continuous iv infusion of TRH for at least 15 days. No clinical improvement was detected. A significant rise of thyroid hormone levels was observed, as well as an upward trend of basal TSH levels and no change of basal PRL and GH levels. TRH acute test-induced TSH and PRL responses became blunted. Treatment provoked also the onset of a responsiveness of PRL to GHRH. The reduced TSH and PRL responses to acute TRH test during treatment could be explained by a down-regulation of TRH pituitary receptors. On the contrary, the onset of PRL responsiveness to GHRH is at present without a satisfactory explanation.     

Different prolactin, thyrotropin, and thyroxine responses after prolonged intermittent or continuous infusions of thyrotropin-releasing hormone in rhesus monkeys

Serum PRL, TSH, and T4 secretion during prolonged continuous or intermittent iv infusions of TRH were studied in 14 adult ovariectomized rhesus monkeys (Macaca mulatta). For 9 days, TRH was administered intermittently at 0.33 or 3.3 micrograms/min for 6 of every 60 min and continuously at 0.33 micrograms/min. With both modes, the PRL levels and responsiveness to TRH simulation peaked on day 1 and then fell to levels that were still higher than the preinfusion values; levels for the intermittently treated group on days 3-9 were 2- to 4-fold above prestimulation levels and significantly (P less than 0.01) higher than levels for the continuously treated group. Elevated basal levels and PRL responses to TRH pulses were similar during the 0.33 and 3.3 micrograms/min pulses of the 9-day treatment period. For both TRH modes, TSH levels were elevated significantly (P less than 0.001) on day 1 [this increase was higher with continuous infusion (P less than 0.001)] and then fell to preinfusion levels by day 3. Serum T4 also increased during both continuous and intermittent TRH stimulations. However, serum T4 levels were significantly lower (P less than 0.01) after intermittent TRH (both 0.33 and 3.3 micrograms/min) than after continuous (0.33 micrograms) TRH (8 +/- 1.1 and 10 +/- 1.8 micrograms T4/dl vs. 18 +/- 3.1 micrograms, respectively). These PRL and T4 responses were replicated when the mode of administering 0.33 micrograms/min TRH was reversed after 9 days. An iv bolus of TRH (20 micrograms) after 9 days of continuous or intermittent TRH infusion caused significant release of PRL and TSH, an indication that neither mode of administration resulted in pituitary depletion of releasable hormone. We have concluded that intermittent TRH is more effective in elevating serum PRL, and continuous TRH is more effective in raising TSH and T4 levels. Thus, the manner of TRH secretion by the hypothalamus may determine its relative physiological importance in the stimulation of lactotropes and thyrotropes.     

The dissociation of the exaggerated prolactin and thyrotropin responses in seminiferous tubule failure following the administration of a double-pulse of thyrotropin-releasing hormone

PRL and TSH secretion has been evaluated in 11 patients with seminiferous tubule failure and 9 controls. When compared to the controls, the patients had increased basal FSH, TSH and PRL levels. However, LH, E2, T and thyroid hormone levels were similar to the controls. Both groups were given two pulses of TRH (200 micrograms) at 30 min intervals. Following the initial pulse of TRH, the patients demonstrated exaggerated TSH and PRL responses. The administration of a second pulse of TRH led to a further increment of TSH secretion in the patients. There was, however, no PRL response to the second TRH pulse in either patients or controls although mean PRL levels remained significantly greater in the patients.     

THE INTERRELATIONSHIPS BETWEEN PROLACTIN AND THYROTROPHIN SECRETION FOLLOWING DOPAMINERGIC BLOCKAGE IN PATIENTS WITH MILD HYPERPROLACTINAEMIA WITHOUT ANY DEMONSTRABLE PITUITARY TUMOUR

PRL, TSH and gonadotrophin responses to the dopaminergic antagonist, metoclopramide, were studied in mildly hyperprolactinaemic patients with normal sella radiology and CT scan. Eleven female patients with basal PRL levels ranging from 23 to 124 ng/ml were challenged with intravenous metoclopramide (10 mg) and on subsequent occasions with TRH (200 micrograms) and LHRH (100 micrograms). On the basis of the PRL secretory pattern following metoclopramide and TRH stimulation, the patients were divided into two groups. Group I comprised six subjects who were PRL non-responsive to TRH and metoclopramide. Group II (five subjects) demonstrated PRL responses to TRH and metoclopramide indistinguishable from female controls. Mean +/- SD basal PRL levels were 68.5 +/- 29.9 ng/ml in Group I and not different in Group II (40.6 +/- 12.0 ng/ml). Basal LH levels were increased in Group II, whereas FSH was increased in Group I. Basal TSH levels were lower in Group I than the controls. Following metoclopramide, Group I patients had an increase in TSH from a basal of 2.4 +/- 0.7 microU/ml to a peak of 5.9 +/- 2.7 microU/ml (P less than 0.005) which occurred at 30 min. TSH values were increased above basal at all time intervals following metoclopramide. In contrast, TSH levels did not change in Group II patients or the controls after metoclopramide administration. Both patient groups had TSH responses to TRH similar to the controls. Following LHRH, the LH increase was greater in Group II and the FSH in Group I. In neither group nor the controls did gonadotrophin levels change after metoclopramide. In Group II females, PRL responsiveness to metoclopramide was associated with TSH non-responsiveness. In Group I females, PRL levels failed to rise, whereas TSH increased. The PRL and TSH profile in Group I females is typical of a prolactinoma. It is concluded that PRL as well as TSH determinations following metoclopramide are useful indices in the assessment of hyperprolactinaemia and may be of value in differentiating the functional state from that of a pituitary tumour.     

A cryptic peptide (160-169) of thyrotropin-releasing hormone prohormone demonstrates biological activity in vivo and in vitro.

TRH is synthesized as a precursor peptide containing five copies of the sequence Gln-His-Pro-Gly, QHPG, flanked by paired basic amino acids, and linked by other peptides. We tested one cryptic peptide, PPT (160-169, SFPWMESDVT), as a possible physiological regulator of pituitary activity in vivo. Male rats were cannulated (jugular) and received a single dose of either PPT or TRH (10(-8)-10(-6) M). PPT caused no consistent effects on either TSH or PRL secretion, while TRH stimulated the secretion of both hormones. However, PPT stimulated a dose-dependent increase in both pituitary TSH beta and PRL mRNA content at 240 min similar to TRH. In primary cultures of rat pituitaries, PPT stimulated a maximum 4-fold increase in TSH beta mRNA and a 2-fold increase in PRL mRNA in 4 h, while TRH increased both TSH beta and PRL mRNA approximately 3-fold. Again, PPT had no significant effect on TSH or PRL secretion into the medium. Thus, PPT appears to be a physiological regulator of both TSH and PRL synthesis, but, unlike TRH, does not act as a secretagogue.     

External pituitary irradiation as a cause of TRH deficiency in patients with pituitary adenomas

The influence of external pituitary irradiation (XRT) on thyrotroph function and PRL secretion was studied in twenty-five patients with pituitary adenomas, of whom eight had acromegaly. Twenty-one patients had undergone subtotal operative removal of their adenomas 8-190 weeks (median 12 weeks) before XRT. Following irradiation there was a significant reduction in peak serum TSH levels in response to i.v. TRH (P less than 0.05, compared with before XRT). Peak TSH levels returned to normal at 3 months. Similarly a transient reduction in TRH-stimulated beta-TSH release was observed. Serum T3 and T4 concentrations also fell after XRT, the levels at 3 months being significantly lower than control values (P less than 0.02), though no difference was seen at 6 and 12 months. A delayed (hypothalamic) serum TSH response to TRH (60 greater than 20-min level) developed at 6 months. In contrast, PRL concentrations (basal and TRH stimulated) were not altered during the 12 months following XRT. These findings demonstrate that thyrotroph function can be transiently impaired following external pituitary irradiation. None of the patients studied required T4 replacement therapy. The development of a delayed TSH response to i.v. TRH may indicate endogenous TRH deficiency. It was not associated with supra-sellar tumour enlargement in our patients and may be due to hypothalamic damage by irradiation.     

Blunted prolactin response to thyrotropin-releasing hormone stimulation in cystinotic children receiving cysteamine

We investigated whether long term cysteamine therapy in cystinotic children altered their basal and stimulated serum PRL levels. Five subjects who had normal plasma PRL responses to TRH stimulation before cysteamine treatment each had a lower basal PRL level and a blunted PRL response during long term (19-59 months) cysteamine therapy. A blunted PRL response was not found in 12 cystinotic subjects of the same age and stage of disease who had not received cysteamine. The effect on PRL release was not found in 2 subjects who received short term (1-2 weeks) treatment with full-dose cysteamine (50 mg/kg . day). The TSH response to TRH stimulation was not blunted during long term cysteamine therapy. These findings suggest that cysteamine alters PRL secretion in humans.     

Growth hormone response to thyrotropin-releasing hormone in diabetes

The effect of TRH on GH secretion was assessed in 13 insulin-dependent diabetics. PRL and TSH responses to TRH were also determined. Glycosylated hemoglobin levels and serial fasting glucose concentrations indicated that all but 1 of the patients had a period of poor diabetic control for several months before the study. Peak PRL and TSH levels after TRH injection in these diabetic patients did not differ significantly from values observed in nondiabetic individuals. Six of the patients responded to TRH with a significant rise in GH levels; basal GH concentrations were also elevated in these patients. Five of the 6 responders and none of the nonresponders had proliferative diabetic retinopathy. The results suggest that diabetics with elevated basal GH levels hyperrespond to TRH, and that nonspecific secretion of GH in response to TRH occurs in some patients with proliferative diabetic retinopathy. Chronic hyperglycemia does not appear to be the critical factor in determining this response.